1. Technical Field
The present invention generally relates to an isolated palonosetron free base, substantially in a solid amorphous form, processes for its preparation, a process for its conversion into pharmaceutically acceptable salts of palonosetron, and pharmaceutical compositions containing the same.
The present invention also provides a palonosetron free base of crystalline form-G, a process for its preparation and process for its conversion into a pharmaceutically acceptable salt thereof; and pharmaceutical compositions containing the same.
2. Description of the Related Art
Palonosetron, also known as (3aS)-2-[(S)-1-azabicyclo[2.2.2]oct-3-yl]-2,3,3a,4,5,6-hexahydro-1-oxo-1H benz[de]isoquinoline, is represented by the structure of Formula I:

Palonosetron hydrochloride is an antiemetic and antinauseant agent and is available in the market under the brand name ALOXI® in the form of injection. Each vial contains palonosetron hydrochloride equivalent to 0.25 mg of base.
U.S. Pat. No. 5,202,333 (“the '333 patent”) discloses 5-HT3 receptor antagonists such as palonosetron and its hydrochloride salt form. The '333 patent further discloses a process for the preparation of 5-HT3 receptor antagonists palonosetron hydrochloride by reduction of 2-(1-azabicyclo[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro-1H-benz[de]isoquinolin-1-one of formula II
using palladium catalyst in acetic acid and perchloric acid. The intermediate was isolated in a semi-solid which was then converted to a hydrochloride salt.
U.S. Pat. No. 5,567,818 (“the '818 patent”) discloses a process for preparing palonosetron hydrochloride by reduction of 2-(1-azabicyclo[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro-1H-benz[de]isoquinolin-1-one using palladium catalyst in toluene and tetrahydrofuran mixture and the resultant palonosetron isolated as its hydrochloride salt. The free base palonosetron was not isolated, but was converted directly into the hydrochloride salt of palonosetron. The '818 patent also discloses reduction of 241-azabicyclo[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro-1H-benz[de]isoquinolin-1-one using palladium catalyst in ethanol and water mixture.
Patent Publication WO2008/146283 (the '283 patent) discloses processes for preparation and purification of palonosetron and salts thereof. The '283 patent discloses isomers of palonosetron designated as Compound A and Compound B.